Intracellular Metabolism of β-L-ddAMP-bis(tbutylSATE), a Potent Inhibitor of Hepatitis B Virus Replication |
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| Authors: | A Faraj L Placidi C Perigaud E Cretton-scott G Gosselin L T Martin |
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| Institution: | 1. Department of Pharmacology , University of Alabama , Birmingham, USA;2. Laboratoire de Chimie Bio-Organique , Universite de Montpellier II , France |
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| Abstract: | Abstract β-L-ddAMP-bis(tbutylSATE) is a potent inhibitor of HBV replication with an EC50 = 0.1 μM. Following a 0-to72-hrs exposure of human hepatocytes to a 10 μM 2′,3′?3H] β-L-ddAMP-bis(tbutylSATE), the pharmacologically active β-L-ddATP was the predominant metabolite attaining a concentration of 268.53 ± 107.97 pmoles/106 cells at 2 hrs. In Hep-G2 cell, β-L-ddATP accounted for 146.8 ± 29.8 pmoles/106 cells at 2 hrs with an half life of approximately 5.4 hrs. This study reveals that extensive intracellular concentrations of β-L-ddATP after incubation of cells to the parent drug is accounting for its potent antiviral activity. |
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